Interferon gamma (IFNg) is an inflammatory lymphokine that has been implicated in the pathogenesis of several inflammatory diseases, including anterior and posterior uveitis. To study the possible role of IFNg in ocular pathogenesis, we generated transgenic mice and rats with constitutive expression of IFNg in the eye. We have extensively characterized both the rat and mouse IFNg transgenic models, and they now constitute a comprehensive and complementary transgenic animal system for studying the in vivo effects of IFN in the eye. In fiscal year 1996, our efforts were directed at investigating the utility of our transgenic rats as a model of posterior and anterior uveitis. We elicited endotoxin-induced uveitis (EIU) in these rats by peripheral administration of lipopolysaccharide (LPS). This resulted in bilateral disruption of the blood-aqueous barrier and acute-onset of anterior uveitis. Compared with wild-type syngeneic rats, a 5- to 10-fold increase in the number of inflammatory cells and protein content of the anterior chamber was observed in the transgenic eyes. Exacerbation of EIU in IFNg transgenic rats suggests that synergy of IFNg with other cytokines secreted during EIU may contribute to the pathology seen in anterior uveitis. EIU in IFNg transgenic rats is characterized by choroiditis and iridocyclitis without retinitis. This clinical feature is similar to certain forms of human posterior uveitis and suggests that these transgenic rats may be a useful model for studying the pathological mechanisms of posterior and anterior uveitis. We also began studying a totally different aspect of IFNg action; its paracrine effects on ocular cells. To characterize the effects of secreted IFNg on resident ocular cells, as often occurs during infection, we cultured retinal pigment epithelia (RPE) and lens epithelial cells in the presence or absence of IFNg. Electrophoretic mobility shift assay (EMSA) and super-shift assays revealed that resident ocular cells respond to IFNg by specifically activating STAT1 and two IFN-inducible negative regulatory transcription factors. Interestingly, interferon consensus sequence binding protein (ICSBP) and interferon regulatory factor 2 (IRF-2) transcription factors are activated in RPE cells, but only ICSBP is activated in the lens epithelial cells.